Serinol (2-amino-1,3-propanediol) is used as an intermediate to make many different fine chemicals, including pharmaceuticals. Examples are iopamidol (U.S. Pat. Nos. 4,001,323, 4,348,377, and 5,035,877); voglibose (European Patent EP 0260121); and dilmapimod (U.S. Publ. 2006/258687). Methods for its manufacture include the catalytic hydrogenation of 1,3-dihydroxyacetone oxime (U.S. Pat. No. 5,922,917); the reaction of nitromethane and formaldehyde (EP 0436414); and the reaction of dihydroxyacetone with hydrazine (CZ 289303).
Another process (U.S. Pat. No. 5,023,379) is a two-step method wherein dihydroxyacetone is mixed with methanol at low temperatures, after which aqueous ammonia is added. Later, Raney nickel is added and hydrogen is introduced under pressure. The reaction mixture is filtered to remove the catalyst, water is removed under vacuum, and serinol is recovered by conversion into the oxalate with oxalic acid dihydrate.
In another synthetic route, 2-nitro-1,3-propanediol sodium salt is hydrogenated in the presence of heavy metal catalysts to produce serinol in high yields, but with the disadvantage of the cost of the catalyst (U.S. Pat. No. 6,509,504). Yet another route uses the expensive starting material, 2-chloro-2-nitro-1,3-propanediol (U.S. Pat. No. 5,053,545).
Another process is the reductive amination of dihydroxyacetone. It has the advantage of producing serinol using inexpensive reactants with a relatively inexpensive catalyst, Raney nickel, but produces byproducts which can be expensive to remove from the serinol (see, for example, WO 9527695). Other, more expensive, catalysts may also be used (JP6009512).
The bis-adduct of serinol, 2,2′-iminobis-1,3-propanediol, is also useful, but generally as an intermediate to produce polymers, including dendrimers (U.S. Pat. No. 6,916,948). It has been produced by the reductive amination of dihydroxyacetone dimer using sodium cyanoborohydride and ammonium chloride in methanol and acetic acid. The product was purified by dissolving the residue in water and introducing the solution to an acidic ion-exchange resin and eluting with water and then aqueous ammonia.
However, the known methods to produce serinol or its bis-adduct are less than desirable due to the cost or toxicity of the reactants or by-products. The present invention provides for the production of either compound, using the same reactants, but varying the process parameters. Surprisingly, the two compounds can be easily separated from each other, resulting in a reduced cost to produce either compound.